ABSTRACT
Retinoblastoma (RB) is the most common primary eye cancer of childhood, affecting approximately 1 in 20,000 live births [1] and accounting for 12% of infant cancer [2]. The disease results from loss or mutation of both alleles of the retinoblastoma gene (RB1). Between 60 and 70% of affected children have sporadic or nonheritable retinoblastoma [1]. In this form of the disease, both RB1 alleles are inactivated somatically in a single developing retinal cell, resulting in unifocal, unilateral tumor development. The remaining 30-40% of affected children have familial or heritable retinoblastoma. These individuals carry an inactivated RB1 allele in their germline, and loss or mutation of the second allele occurs somatically. In the great majority of kindreds, heritable RB is characterized by virtually complete penetrance (nearly all carriers develop the disease) and high expressivity (disease is characterized by multifocal, bilateral tumor development). In some kindreds, however, the disease demonstrates reduced penetrance and expressivity (‘‘lowpenetrance RB’’). Penetrance may be as low as 20% in these kindreds, and affected carriers often have only unilateral RB or benign retinal lesions (called retinoma or retinocytoma) [3-7]. It is estimated that between 10 and 15% of children with unilateral RB harbor a mutant allele in their germline [1,8,9].
